Mechanical fluidity of fully suspended biological cells

Mechanical characteristics of single biological cells are used to identify and possibly leverage interesting differences among cells or cell populations. Fluidity---hysteresivity normalized to the extremes of an elastic solid or a viscous liquid---can be extracted from, and compared among, multiple rheological measurements of cells: creep compliance vs. time, complex modulus vs. frequency, and phase lag vs. frequency. With multiple strategies available for acquisition of this nondimensional property, fluidity may serve as a useful and robust parameter for distinguishing cell populations, and for understanding the physical origins of deformability in soft matter. Here, for three disparate eukaryotic cell types deformed in the suspended state via optical stretching, we examine the dependence of fluidity on chemical and environmental influences around a time scale of 1 s. We find that fluidity estimates are consistent in the time and the frequency domains under a structural damping (power-law or fractional derivative)model, but not under an equivalent-complexity lumpedcomponent (spring-dashpot) model; the latter predicts spurious time constants. Although fluidity is suppressed by chemical crosslinking, we find that adenosine triphosphate (ATP) depletion in the cell does not measurably alter the parameter, and thus conclude that active ATP-driven events are not a crucial enabler of fluidity during linear viscoelastic deformation of a suspended cell. Finally, by using the capacity of optical stretching to produce near-instantaneous increases in cell temperature, we establish that fluidity increases with temperature---now measured in a fully suspended, sortable cell without the complicating factor of cell-substratum adhesion

The Effect of Heroic Medical Care on Mission Medical Outcomes

Study Objective: A catastrophic medical event depletes medical resources. What happens to the rest of the missions medical outcomes after such an event? Use Probabilistic Risk Assessment (PRA) to see if we can find out. What is the Integrated Medical Model? PRA model using Monte Carlo methodology; Used to assess mission risk due to in-flight medical events; User defined Design Reference Missions (DRM) (crew, duration, EVA (Extra-Vehicular Activity), etc.); Considers outcomes for 100 medical conditions that have or may occur in-flight; 100,000 trials conducted per DRM

Enabling Space Exploration Medical System Development Using a Tool Ecosystem

The NASA Human Research Program's (HRP) Exploration Medical Capability (ExMC) Element is utilizing a Model Based Systems Engineering (MBSE) approach to enhance the development of systems engineering products that will be used to advance medical system designs for exploration missions beyond Low Earth Orbit. In support of future missions, the team is capturing content such as system behaviors, functional decompositions, architecture, system requirements and interfaces, and recommendations for clinical capabilities and resources in Systems Modeling Language (SysML) models. As these products mature, SysML models provide a way for ExMC to capture relationships among the various products, which includes supporting more integrated and multi-faceted views of future medical systems. In addition to using SysML models, HRP and ExMC are developing supplementary tools to support two key functions: 1) prioritizing current and future research activities for exploration missions in an objective manner; and 2) enabling risk-informed and evidence-based trade space analysis for future space vehicles, missions, and systems. This paper will discuss the long-term HRP and ExMC vision for the larger ecosystem of tools, which include dynamic Probabilistic Risk Assessment (PRA) capabilities, additional SysML models, a database of system component options, and data visualizations. It also includes a review of an initial Pilot Project focused on enabling medical system trade studies utilizing data that is coordinated across tools for consistent outputs (e.g., mission risk metrics that are associated with medical system mass values and medical conditions addressed). This first Pilot Project demonstrated successful operating procedures and integration across tools. Finally, the paper will also cover a second Pilot Project that utilizes tool enhancements such as medical system optimization capabilities, post-processing, and visualization of generated data for subject matter expert review, and increased integration amongst the tools themselves

Engineering Biological Materials for Carbon Capture and the Electrochemical Reduction of Carbon Dioxide to Light Hydrocarbons

Decarbonization of the global economy will require the identification of substitute carbon sources for the production of fuels, plastics, textiles, pharmaceuticals, and other products that are derived from fossil carbon. The gigaton scale of carbon dioxide emissions necessitates the development of better materials for its capture, yet offers the opportunity to use purified carbon dioxide gas as an input to the electrochemical carbon dioxide reduction reaction. This reaction combines carbon dioxide, water, and electricity in the presence of specialized catalysts to create light hydrocarbons such as methane, ethanol, and ethylene, precursors critical to many of the products that power the modern economy. In this thesis, I present a range of biological materials capable of capturing carbon dioxide and catalyzing its conversion to products. First, catalysts made from genetically-engineered M13 bacteriophage are light-crosslinked and metallized to create copper electrodes that explore the effect of pore structure on catalyst performance. Second, catalysts made via copper electrodeposition are modified by viral proteins to create nanostructured, crystalline electrodes that shift product distributions towards C1 hydrocarbons like formate and methane. Third, catalysts made from biological carbon nanofibers template copper nanoparticles that increase catalyst activity and generate product distributions on par with copper catalysts found in the literature. Fourth, amine resins templated on the surface of engineered M13 bacteriophage produce high-surface-area materials capable of carbon dioxide capture and release. Additionally, I exposit reaction systems for maximizing gas availability and reaction stability for single- and double-sided electrodes in carbon dioxide electroreduction. The biological catalysts and membranes described here provide structure/performance information to advance the design of specialized catalysts and membranes for the sustainable creation of hydrocarbon products from atmospheric carbon dioxide.Ph.D

Mechanical Fluidity of Fully Suspended Biological Cells

Mechanical characteristics of single biological cells are used to identify and possibly leverage interesting differences among cells or cell populations. Fluidity—hysteresivity normalized to the extremes of an elastic solid or a viscous liquid—can be extracted from, and compared among, multiple rheological measurements of cells: creep compliance versus time, complex modulus versus frequency, and phase lag versus frequency. With multiple strategies available for acquisition of this nondimensional property, fluidity may serve as a useful and robust parameter for distinguishing cell populations, and for understanding the physical origins of deformability in soft matter. Here, for three disparate eukaryotic cell types deformed in the suspended state via optical stretching, we examine the dependence of fluidity on chemical and environmental influences at a timescale of ∼1 s. We find that fluidity estimates are consistent in the time and frequency domains under a structural damping (power-law or fractional-derivative) model, but not under an equivalent-complexity, lumped-component (spring-dashpot) model; the latter predicts spurious time constants. Although fluidity is suppressed by chemical cross-linking, we find that ATP depletion in the cell does not measurably alter the parameter, and we thus conclude that active ATP-driven events are not a crucial enabler of fluidity during linear viscoelastic deformation of a suspended cell. Finally, by using the capacity of optical stretching to produce near-instantaneous increases in cell temperature, we establish that fluidity increases with temperature—now measured in a fully suspended, sortable cell without the complicating factor of cell-substratum adhesion.Singapore-MIT Alliance for Research and TechnologyNational Science Foundation (U.S.). Faculty Early Career Development (CAREER) Program (CBET-0644846))National Institutes of Health (U.S.). Molecular, Cell, and Tissue Biomechanics (Training Grant EB006348

Burn care in the Greek and Roman antiquity

The last century brought about more rapid new developments in the treatment of burns, which significantly lowered the mortality of burn injuries. However, burns were already treated in antiquity, where the threshold from spirituality to scientific medicine originated. The existing literature on burn treatment is very limited and there are many cross-references, some of them incorrect. The aim of this work by an interdisciplinary team of historians and physicians is to offer a more precise reproduction of the burn treatment of Greek and Roman antiquity using original texts in context and with a modern scientific background. There are many sources from ancient doctors on the subject of burn treatment, as well as the treatment of burned-out wounds and frostbite, which have not yet been mentioned. The literature research also showed an understanding of scientific contexts in ancient medicine, such as antiseptics or rheology. Interestingly, there was a change in burn medicine from everyday Greek medicine to Roman military medicine with other burn patterns. The care of patients using analgetics and the therapy of burn shock arose from the literature. The ancient world is considered to be the foundation of medicine, but it is believed to have been based mainly on shamanism rather than science. However, already more than two millennia ago, burns were correctly assessed and treated according to today’s scientific standards and scientific relationships were recognized

Prediction of Malignant Middle Cerebral Artery Infarction by Magnetic Resonance Imaging Within 6 Hours of Symptom Onset: A Prospective Multicenter Observational Study

Objective: Early identification of patients at risk of space-occupying malignant middle cerebral artery (MCA) infarction (MMI) is needed to enable timely decision for potentially life-saving treatment such as decompressive hemicraniectomy. We tested the hypothesis that acute stroke magnetic resonance imaging (MRI) predicts MMI within 6 hours of stroke onset. Methods: In a prospective, multicenter, observational cohort study patients with acute ischemic stroke and MCA main stem occlusion were studied by MRI including diffusion-weighted imaging (DWI), perfusion imaging (PI), and MR-angiography within 6 hours of symptom onset. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI. Results: Of 140 patients included, 27 (19.3%) developed MMI. The following parameters were identified as independent predictors of MMI: larger acute DWI lesion volume (per 1 ml odds ratio [OR] 1.04, 95% confidence interval [Cl] 1.02-1.06; p 82 ml predicted MMI with high specificity (0.98, 95% Cl 0.94-1.00), negative predictive value (0.90, 0.83-0.94), and positive predictive value (0.88, 0.62-0.98), but sensitivity was low (0.52, 0.32-0.71). Interpretation: Stroke MRI on admission predicts malignant course in severe MCA stroke with high positive and negative predictive value and may help in guiding treatment decisions, such as decompressive surgery. In a subset of patients with small initial DWI lesion volumes, repeated diagnostic tests are required. ANN NEUROL 2010;68:435-44